N-Halogenomethyl derivatives of bis-hydantoins

ABSTRACT

N-Halogenomethyl derivatives of bis-hydrantoins, which are reactive partners for condensation reactions, in particular with alkyl esters of phosphorous acid to the dialkoxyphosphonomethyl derivatives. These latter compounds can be used as additives in plastics to confer non-inflammability. The preparation and use of the N-halogenomethyl derivatives are described.

United States Patent [1 1 Habermeier et al.

[ Oct. 28, 1975 N-HALOGENOMETHYL DERIVATIVES OF BIS-HYDANTOINS [75]Inventors: Jiirgen Habermeier, Pfeffingen;

Daniel Porret, Fresens, Ne, both of Switzerland [73] Assignee:Ciba-Geigy Corporation, Ardsley,

[22] Filed: Feb. 7, 1975 [21] Appl. No.: 548,049

Related US. Application Data [63] Continuation-impart of Ser. No.341,640, March 15,

1973, abandoned.

[30] Foreign Application Priority Data Apr. 4, 1972 Switzerland 4892/72[52] US. Cl..... 260/309.5; 260/306 R; 260/45.7 P; 260/458 N [51] Int.Cl. C07F 9/65 [58] Field of Search 260/3095 [56] References Cited OTHERPUBLICATIONS Behrend et al., Liebigs Annal. Chemie, Vol. 365, pp. 38-49drawing (1909).

Long et al., J. Amer. Chem. Soc. Vol. 70, pp. 900 903, (1948).

Schlogl et al., J. Med. Chem. Vol. 4, pp. 231 & 256 relied on (1961).

Primary Examiner-Natalie Trousof Attorney, Agent, or Firm-Luther A. R.Hall [5 7] ABSTRACT N-Halogenomethyl derivatives of bis-hydantoins,

6 Claims, No Drawings N-HALOGENOMETHYL DERIVATIVES OF BlS-HYDANTOINS Theinvention relates to chloromethylhydantoins and bromomethylhydantoins aswell as chloromethyldihydrouracils and bromomethyldihydrouracils andprocesses for the manufacture of these compounds.

The chloromethylhydantoins and bromomethylhydantoins are crystalline,very hygroscopic substances which are hydrolysed even by atmospherichumidity. They are very reactive partners for condensation reactions.

Whilst German Offenlegungsschrift No. 2,064,474 has disclosed3-halogenomethyldantoins substituted in the l-position, these compoundssuffer from the disadvantage that they only possess a single reactivegroup.

The compounds according to the invention have the following formula I orI:

wherein Z denotes a nitrogen-free divalent radical which is required tocomplete a five-membered or sixmembered heterocyclic ring, Y denotes adivalent aliphatic, cycloaliphatic or araliphatic radical and X denoteschlorine or bromine.

Z preferably represents a methylene group which can be substituted byalkyl groups with one to six carbon atoms or by a cycloalkylidene group.Z can be especially the iso-propylidene group, also the norisopropylmethylene group, the cyclohexylidene group or thecyclopentylidene group. Furthermore, Z can also denote an ethylene groupoptionally substituted by alkyl groups with one to four carbon atoms,such as the ethylene group, the 1,2-dimethyl-ethylene group, the2,2-dimethyl-ethylene group or the l-methyl 2-isopropyl-ethylene group.

Y in the formula 1 preferably denotes an alkylene group, such as themethylene, ethylene, butylene, hexylene or dodecylene group, or analkylene group interrupted by oxygen atoms, such as 3-oxapentamethylene.

The new compounds are valuable partners for condensation reactions,since they possess two reactive groups one halogenomethyl group and onereactive hydrogen, or two halogenomethyl groups. They can condense withalcohols, phenols and the like, and in particular also with alkyl estersof phosphorous acid to give dialkoxyphosphonomethylhydantoins ordialkoxyphosphonomethyldihydrouracils. These compounds can be used, forexample, as additives in plastics, to confer non-inflammability.

The bis-hydantoin derivatives of this invention possessing twochloromethyl groups can react with bisphenols to prepare high molecularweight aromatic polyethers having useful high temperature properties. W.R. Sorenson and T. W. Campbell, Preparative Methods of PolymerChemistry, 2nd Edition, lnterscience Publishers, New York, 1968, pp.-182 relate the preparation of aromatic polyethers derived frombis-phenol A.

A prime objective of this invention relates to the preparation ofN-halogenomethyl derivatives of hydantoin as intermediates in thepreparation of the corresponding N-dialkoxyphosphonomethyl derivativesof hydantoin which in turn are useful flame retardants for a variety ofpolymeric systems. The N-halogenomethyl derivatives are directlyconverted to the corresponding phosphonate esters usingphosphite esters,such as triethyl phosphite, in the well-known Arbuzov reaction.

The phosphonate esters attached to hydantoin moieties are particularlyuseful as flame retardants possessing as they do both nitrogen andphosphorus. The particularly efficacious activity as flame retardants ofcertain molecules containing both nitrogen and phosphorus is well-knownas described by J. W. Lyons, The Chemistry and Uses of Fire Retardants,Willey- Interscience, New York, 1970, pp. 20-21, 189,354-357.Phosphonates are widely useful as flame retardants in many polymericsystems including cellulosics ibid, pp. 184-189, polyurethanes, pp.354-357, and polyesters, pp. 373-374, 398-401. In the latter case thephosphonates are often incorporated into polyester melts where theyself-polymerize and tranesterify with the polyester involved. Thephosphonate esters made from the N-halogenomethyl derivatives ofbis-hydantoins of this invention are useful as flame retardants in avariety of polymeric systems.

The N-halogenomethyl derivatives of this invention are manufacturedaccording to methods which are in themselves known by reacting thecorresponding, in part known, N-hydroxymethylhydantoins orN-hydroxymethyldihydrouracils of the formula [1 or II.

HN N-CH2OH 11) with compounds which introduce chlorine or bromine,especially with acid halides, preferably inorganic acid halides such asSOCl or SOBr PCl PCl PBr POCl and the like, as well as organic acidchlorides such as oxalyl chloride, are also suitable for this purpose. Afurther possibility is the action of hydrogen chloride or hydrogenbromide on the N-hydroxymethyl compounds. The latter are obtained byaddition of formaldehyde to the corresponding cyclic ureides.

EXAMPLE 1 3-Chloromethyl-5,S-dimethylhydantoin A mixture of 474 g oftechnical 3-hydroxymethyl- 5,5-dimethylhydantoin (3 mols), 500 ml ofchloroform and 0.8 ml of pyridine is stirred at 50C in a dry glassapparatus equipped with a stirrer, thermometer, dropping funnel andreflux condenser with gas outlet. A solution of 428.4 g of thionylchloride (3.6 mols) in 500 ml of chloroform is added dropwise to thecolourless suspension over the course of 1.5 hours at 5055C reactiontemperature. A clearsolution is thereby pro- EXAMPLE 2 3-Chloromethyl-5,5pentamethylenehydantoin A mixture of 238 g of 3-hydroxymethyl-5,5-pentamethylenehydantoin (1.2 mols), 300 ml of dioxane and 0.6 ml ofpyridine is stirred at 62C in accordance with Example 1. Under theseconditions, the bulk of the hydantoin derivative dissolves. A solutionof 164.2g of thionyl chloride (1.38 mols) in 180 ml of dioxane is addeddropwise over the course of 1.75 hours, whilst stirring. Thereafter themixture is stirred for a further 6 hours at 65C; towards the end of thistime, S and HCl are expelled by blowing in nitrogen.

Working up takes place according to Example 1 and 254.2 g (97.7% oftheory) of a light ochre-coloured crystal powder melting at l66-170C areobtained. The product can be purified by recrystallisation, for examplefrom anhydrous acetone. It then melts at 174-176C. The chlorine contentis then 14.8% (corresponding to 90.5% of theory). The proton-magneticresonance spectrum (100 Mc-H-NMR, recorded in deuterochloroform (DClagainst tetramethylsilane (TMS) shows, through the following signals,that 3- chloromethyl- 1 ,3-diazaspiro-(4.5 )-decan e-2,4-dione of thestructure shown below has been produced.

Multiplet at 8 1.35-2.2 methylene protons of the six-membered ringSinglet at 8 5.25 N CH C1 Singlet at 8 7.75 N H EXAMPLE 33-Chloromethyl-5,S-dimethylhydantoin A solution of 1,186 g ofindustrially produced 3- hydroxymethyl-S,S-dimethylhydantoin (7.5 mols)in 1,500 ml of dioxane is stirred at 60C in an apparatus according toExample 1. 3.75 ml of pyridine are added to the clear solution and thena solution of 1,026 g of thionyl chloride (8.62 mols) in 1,125 ml ofdioxane is added dropwise over the course of 50 minutes at 60C, whilststirring. The reaction is slightly exothermic so that the heating bathis removed periodically. After the dropwise addition, the mixture isstirred for a further 5 hours at 60C. Thereafter it is concentrated toconstant weight at 60C/ 15 mm Hg and a dark yellow crystal mass isobtained in quantitative yield. The resulting crude product is purifiedby crystallising it from a mixture of 350 ml of dioxane and 2,500 ml ofpetroleum ether. After drying, 1,034 g (78% of theory) of colourless,needle-shaped crystals melting at 132.4 C are obtained (Mettler Fp 51;0.lC/Minute).

The elementary analysis gives the following values:

The proton-magnetic resonance spectrum (60 Mc- H-NMR in CDCl againstTMS) shows, through the following signals, that the structure givenbelow is correct.

6 a 150('l) \c/cHa protons: sing et CH 2 protons: 6 5.30 (singlet) ClCHN l proton: 6 6.87.2 (multiplet) N-H CH; O

HN v N--CH C1 EXAMPLE 4 3-Bromomethyl-5 ,S-dimethylhydantoin Analogouslyto Example 3, a mixture of 173.9 g of technical3-hydroxymethyl-5,5-dimethylhydantoin 1.1 mols) and 400 m1 of dioxane isreacted, after the addition of 2 ml of pyridine, over the course ofminutes with a solution of 250 g of thionyl bromide (1.203 mols) in 300ml of dioxane at 50C, whilst stirring. Thereafter, the mixture isstirred for a further 4 hours at C. It is then concentrated to drynessat 70C/20 mm Hg and dried to constant weight at 0.3 mm Hg/70C. Ayellowish crystal paste is obtained in quantitative yield. I

This paste is treated with a mixture of 400 ml of diethyl ether and mlof hexane and the mixture is filtered after 30 minutes. The product isdried at 20C over P 0 under 12 mm Hg. 126 g (without working up themother liquor) of a light ochre coloured crystal- 1 'ane/methylenechloride (2:1) and subsequently from dioxane/benzene (1:1 A colourlesscrystal powder is .5 6 obtained, which melts at l15116.5C and proves tomm Hg yields a colourless,- crystalline distillate which be extremelyhygroscopic and easily hydrolysable. after solidification shows amelting point of The elementary analysis shows: l91l95C.

Elementary analysis:

found: calculated:

I: I: found: calculated 33.0% Br 36.15% Br 42] C 417517 C 4.93% H 4.97%H 15.28% N 15.34% N The purity, with respect to bromine content, is91.3% 907% CI 19417 C] of theory.

The protonmagnetic resonance spectrum (100 McH-NMR in CDC1 against TMS)shows the foll5 lowing signals: The product has the following structure:

c H3 C H 3 0 O H c CH CLCH -N\ /NCH N\ NCH CL C C II ll 0 5 1.42(singlet) EXAMPLE 6 5 g 3.3'-Hexamethy1ene bis 5 71 (singlet)lChl0romethyl-5,S-dimethyldantoin 7 This proves that 3 br0mOmethy] 5,5 Asolution of 250g of thionyl chloride (0.1 mol) and 30 ml of dioxane isadded dropwise over the course dimethylhydantom of the followingstructure has been O 1 reduced, of 55 minutes, at 60 C, to a mixture of39.8 g of 3,3 p hexamethylene bis-( 1hydroxymethy1-5,5-

dimethylhydantoin) (0.10 mol), 40 ml of dioxane and CH 0 0.1 ml ofpyridine, analogously to Example 1. After 9 H C hours at 60C, thereaction is complete and working up 3 takes place according toExample 1. The product is HN 2 dried at 120C/0.2 mm Hg. 42.8 g of ayellow clear, 40 highly viscous product having a chlorine content of g14.81% of chlorine (91.1% of theory) are obtained.

A crude product distilled in a bulb tube at 185C/0. 14 mm Hg gives apale yellowish, highly vis- EXAMPLE 5 cous distillate showing thefollowing analytical data:

3,3-Methy1ene bis( 1-ch1oromethy1-5,5-dimethyldantoin) found:calculated: A solution of 27.3 of thionyl chloride (0.23) and 30 1 C 1 Cml of dioxane is added dropwise, over the course of 70 s 648% H minutes,to a mixture of 37.8 g of 3,3'-methy1ene bis- {112 1 C] 233: E1-hydroxymethy1-5,S-dimethylhydantoin) (0. 1 15 mol), 40 ml of dioxaneand 0.1 ml pyridine, analogously to Example 1. Thereafter the mixture isstirred The product has the following structure:

CH CH II ll 0 O for a further 9 hours at C. The solution is then con-APPLICATION EXAMPLES centrated at C/20 mm Hg and dried to constant 5weight at C/0.3 mm Hg. 41.3 g ofa brownish, crys- EXAMPLE I tallineproduct (98.4% of theory) having a chlorine content of 18.3% of chlorineand a melting point of 187C193C are obtained.

A crude product distilled in a bulb tube at C/0.2 A solution of 228.3 gof bisphenol A (1.0 mol) in Condensation of3-chloromethy1-5,S-dimethylhydantoin with bisphenol A 1,500 ml ofdioxane is stirred at 25C and 46 g of sodium metal (2.0 mols) are addedin pieces. The sodium dissolves, with evolution of hydrogen. To completethe reaction, the mixture is stirred at 100C reaction temperature untilall the sodium has dissolved. A very thick paste is therebyproduced.Thereafter a solution of 371 g of the 3-chloromethylhydantoin (2.1 mols)manufactured according to Example 3 in 1.500 ml of dioxane is addeddropwise over the course of 45 minutes at 98-l00C whilst stirring. Thepaste is thereby converted into a thin, yellow suspension. After thedropwise addition, the suspension is stirred for a further 15 hours at100C. It is then cooled to 60C and the sodium chloride produced isfiltered off. The mixture is then concentrated to dryness at 50C/ I 5 mmHg and is dried to constant weight at 50C/0.l5 mm Hg.

509 g of a light ochre-coloured crystalline body (100% of theory)melting at 56C (Mettler FP5l at l/minute) are thus obtained.

The proton-magnetic resonance spectrum (60 Mc-H- NMR in CDCl againstTMS) shows, through the presence of the signals for Ar-C having thestructure shown below is about 90% pure.

peated with ml of toluene. Finally, the material is dried to constantweight at 60C.

140 g (92.4%) of a crude diglycidyl compound which 'is highly viscousand clear but of a light brown colour Flexural strength (VSM 77.l03)l5-l7 kg/mm Deflection (VSM 77.103) 5-8.6 mm

Impact strength (VSM 77.]05) l0-l6 5 cm.

kg/cm Heat distortion (DIN 53,461) l20-l2lC Water absorption (4days/20C) 0.34%

EXAMPLE ll 192.5 g of a suspension of sodium-cyclopentadiene in toluene,of about 22.9% (0.5 mol) strength, is treated dropwise at 60C, whilststirring, with a solution of 88.3 g of the3-chloromethyl-5,S-dimethylhydantoin manufactured according to Example 3(0.5 mol) in 350 ml of dioxane. After the dropwise addition, the mixtureis stirred for a further 15 hours at 90.

Thereafter, the sodium chloride produced is filtered off hot and thesolution is concentrated to dryness at 60C/20 mm Hg. The residue is thendried to constant weight at 60C/0.2 mm Hg.

79.0 g of a red-brown powder melting at 205.3C Mettler FP51: 10C/minute)are obtained.

CH CH O sn p-1 3 i -Tcr-g H-N -CH -o@-c o-ca 9 2 l 2 c H GlycidylationThe material is purified by recrystallisation from 124 g of thebis-hydantoin (0.244 mol) are stirred chloroform/hexane. A light brownproduct which melts with 452 g of epichlorohydrin (4.88 mols) and 1.6 gof 50 at 2l5.3C (Mettler FP51: 1C/minute) is obtained.

50% strength aqueous tetramethylammonium chloride solution for 0.75 hourat 90C and are thereafter subjected to an azeotropic circulatorydistillation at 60C which is adjusted so that at 140C bath temperaturean internal temperature of 60C results (vacuum 50-85 mm Hg) and thatrapid distillation occurs. 44.9 g of 50% aqueous sodium hydroxidesolution are then added dropwise over the course of 2 hours whilst thewater present in the reaction mixture is continuously removedazeotropically and separated off. Distillation is continued for about afurther 45 minutes and the mixture is then cooled to 40C. The sodiumchloride produced in the reaction is removed by suction filtration andthe organic phase is washed with 80 ml of water. The organic phase isthen concentrated completely (60C/2O mm Hg), 50 ml of water are addedand all, the volatile constituents are again distilled off, under theconditions mentioned; the same is subsequently re- What is claimed is:l. A halogenomethyl bis-hydantoin of the formula wherein Z denotesmethylene optionally substituted with alkyl of one to six carbon atomsor Z denotes cycloalkylidene of five to six carbon atoms,

Y denotes alkylene, of one to 12 carbon atoms 3- oxapentamethylene, and

X denotes chlorine orb omine.

2. A compound according to claim 1 wherein Y de- 9 notes alkylene of oneto six carbon atoms or 3- 5. A Compound according to claim 3 which is3,3- oxapentamethylene. methylene bis(l-chloromethyl-5,S-dimethylhydantoin.

3. A compound according to claim 1 wherein 2 de- 6. A compound accordingto claim 3 which is 3,3- notes isopropylidene. hexamethylene bis(l-chloromethyl-S ,5-

4. A compound according to claim 1 wherein Z de- 5 dimethylhydantoin.

notes acyclohexylidene group.

1. A HALOGENOMETHYL BIS-HYDANTOIN OF THE FORMULA
 2. A compound accordingto claim 1 wherein Y denotes alkylene of one to six carbon atoms or3-oxapentamethylene.
 3. A compound according to claim 1 wherein Zdenotes isopropylidene.
 4. A compound according to claim 1 wherein Zdenotes a cyclohexylidene group.
 5. A compound according to claim 3which is 3,3''-methylene bis(1-chloromethyl-5,5-dimethylhydantoin.
 6. Acompound according to claim 3 which is 3,3''-hexamethylenebis(1-chloromethyl-5,5-dimethylhydantoin.